Oxygen plays a significant role in wound healing, and maintaining elevated tissue oxygenation levels are an important factor in the dermal healing response. Specifically, non-healing diabetic chronic wounds (defined as lasting > 6 weeks) often show devastatingly low oxygen concentrations, as low as 5 mmHg oxygen partial pressure. In the USA, there are more than 29.1 million diabetics, with 1.7 million new cases every year. About 3-4 million new diabetic ulcers are diagnosed every year, and these numbers are increasing as our population ages. It is estimated that up to 25% of all diabetics will develop a foot ulcer, and a fifth of these cases will result in a chronic non-healing wound that requires amputation. Oxygen treatment has been demonstrated to promote chronic wound healing by enhancing metabolism, extracellular matrix synthesis, and neovascularization, all while limiting antimicrobial activity. Despite the benefits of supplemental oxygen, current oxygen delivery therapies are intermittent, inconvenient for the patient, and require access to expensive and specialized equipment. Hence, there is a significant need for a simple, low-cost wound dressing able to support regenerative levels of oxygen and to supplement or possibly supplant current therapies (hyperbaric oxygen, topical oxygen via tent/bag). This proposal provides a unique polymerized chitosan hydrogel sheet dressing that has the potential to provide uniform and tunable oxygenation across an ulcerous chronic wound. A biocompatible photocrosslinkable chitosan hydrogel covalently modified with perfluorocarbons (PFCs) has been invented. The wound dressing made from the hydrogel will be marketed under the name OXAID(tm) through the company O2 RegenTech LLC. OXAID uniquely allows for the creation of sheet hydrogels that covalently incorporate PFCs for sustained oxygenation for up to five days at significant oxygen partial pressures. Thus, OXAID potentially marries the benefits of oxygen treatment (above) with hydrogel dressings (increased angiogenesis, enhanced autolytic debridement, increased re-epithelialization). The primary goal of this project is to obtain proof that OXAID is safe and can deliver oxygen to effectively heal chronic wounds. The primary hypothesis is that the oxygen-loaded fluorinated hydrogel platform will provide both enhanced dermal healing responses significantly faster and more completely than both unoxygenated controls and a commercial sheet hydrogel dressing. To test this overall hypothesis, the Specific Aims are: 1. Scale up OXAID synthesis and characterize chemical and material properties; and 2. Conduct a pre-clinical in vivo feasibility study to evaluate the safety and efficacy of OXAID for diabetic chroni wound healing.